Child and Adolescent Psychiatry: Update on the Antidepressant Controversy

The FDA recently issued a public health advisory requiring
manufacturers of all antidepressant medications to
add a black box warning about increased suicidality
in pediatric patients. Since that time, however, a number
of clinically important studies that further address this issue
have been published. A brief review of the data follows.

Although the FDA analysis focused on antidepressant treatment trials, Bridge and colleagues1 examined the incidence of emergent suicidality in a psychotherapy treatment trial for adolescent depression. In this clinical trial of psychotherapy, depressed adolescents were randomized to receive cognitive-behavioral therapy, systemic behavioral family therapy, or nondirective supportive therapy over a period of 12 to 16 weeks. No adolescents received antidepressant medication during the course of the trial. The incidence of emergent suicidality was assessed in 88 of the depressed patients who denied suicidality at the time of the clinical intake interview.

Suicidality developed in 11 (12.5%)
of these adolescents during treatment.
Of those, 10 had suicidal ideation without
a plan, and 1 made a suicide attempt.
Most of the episodes of suicidality
occurred within 3 weeks of beginning
therapy. The investigators concluded that
the rate of emergent suicidality was similar
to the rates in pharmacotherapy trials
of depressed youths.

Simon and colleagues2 conducted a study to evaluate the risk of serious suicide attempt and suicide death in relation to initiation of antidepressant treatment. These investigators used computerized health plan records to identify 65,103 patients who received antidepressant treatment between 1992 and 2003. Death certificates were used to identify those who had died by suicide. A serious suicide attempt was defined as an attempt that led to hospitalization, which was identified by using hospital discharge data. The age of patients included in the sample ranged from 5 to 105 years (mean, 44 years).

The investigators determined that
the highest risk of suicidality occurred
in the month before treatment initiation,
particularly in the week before
starting antidepressant medication. In
both adults and adolescents, there was
a swift decline in suicide attempts immediately
after starting medication treatment
and a gradual decline over the next
6 months. The risk of death by suicide
did not increase during the first month
of antidepressant treatment and remained
constant throughout the first 6
months of treatment.

These investigators also compared
suicidal risk associated with older antidepressants
and with 1 of the 10 newer
antidepressants included in the FDA
warning. The older antidepressants,
primarily tricyclics and trazodone, were
associated with a higher risk of suicidality
in the first month of treatment;
this was not the case for the newer antidepressants.
The authors concluded that
the available data do not demonstrate
an increased risk of suicide or serious
suicide attempt after initiation of antidepressant
medication, and that the risk
is not higher for those treated with newer
antidepressants. Based on their findings,
Simon and colleagues raised concern that
the FDA warnings about antidepressants
and emergent suicidality may discourage
depressed persons from obtaining
needed clinical treatment.

One of the most comprehensive and thoughtful articles on the risks versus benefits of antidepressant treatment for children and adolescents with depression was authored by Bridge and colleagues.3 These investigators reviewed the FDA analysis of antidepressant medication and pediatric suicidality in major depressive disorder. It is important to remember that the increased risk of suicidality found in the FDA analysis of antidepressant trials consisted predominantly of suicidal ideation and less frequently of suicide attempts. There were no completed suicides in these trials.